High prevalence of respiratory ciliary dysfunction in congenital heart disease patients with heterotaxy.

Circulation 2012 May 12;125(18):2232-42. Epub 2012 Apr 12.

Department of Developmental Biology, University of Pittsburgh School of Medicine, 530 45th St, Pittsburgh, PA 15201, USA.

Background: Patients with congenital heart disease (CHD) and heterotaxy show high postsurgical morbidity/mortality, with some developing respiratory complications. Although this finding is often attributed to the CHD, airway clearance and left-right patterning both require motile cilia function. Thus, airway ciliary dysfunction (CD) similar to that of primary ciliary dyskinesia (PCD) may contribute to increased respiratory complications in heterotaxy patients.

Methods And Results: We assessed 43 CHD patients with heterotaxy for airway CD. Videomicrocopy was used to examine ciliary motion in nasal tissue, and nasal nitric oxide (nNO) was measured; nNO level is typically low with PCD. Eighteen patients exhibited CD characterized by abnormal ciliary motion and nNO levels below or near the PCD cutoff values. Patients with CD aged >6 years show increased respiratory symptoms similar to those seen in PCD. Sequencing of all 14 known PCD genes in 13 heterotaxy patients with CD, 12 without CD, 10 PCD disease controls, and 13 healthy controls yielded 0.769, 0.417, 1.0, and 0.077 novel variants per patient, respectively. One heterotaxy patient with CD had the PCD causing DNAI1 founder mutation. Another with hyperkinetic ciliary beat had 2 mutations in DNAH11, the only PCD gene known to cause hyperkinetic beat. Among PCD patients, 2 had known PCD causing CCDC39 and CCDC40 mutations.

Conclusions: Our studies show that CHD patients with heterotaxy have substantial risk for CD and increased respiratory disease. Heterotaxy patients with CD were enriched for mutations in PCD genes. Future studies are needed to assess the potential benefit of prescreening and prophylactically treating heterotaxy patients for CD.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.111.079780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770728PMC
May 2012
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References

(Supplied by CrossRef)
Heterotaxy and complex structural heart defects in a mutant mouse model of primary ciliary dyskinesia
Tan SY et al.
J Clin Invest 2007

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